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Title: RANK links senescence to stemness in the mammary epithelia, delaying tumor onset but increasing tumor aggressiveness
Author: Benítez, Sandra
Cordero, Alex
Santamaría, Patricia G.
Redondo Pedraza, Jaime
Rocha, Ana S.
Collado-Solé, Alejandro
Jimenez, Maria
Sanz Moreno, Adrian
Yoldi, Guillermo
Santos, Juliana C.
Benedictis, Ilaria De
Gómez Aleza, Clara
Silva Álvarez, Sabela Da
Troulé, Kevin
Gómez López, Gonzalo
Alcazar, Noelia
Palmero, Ignacio
Collado, Manuel
Serrano Marugán, Manuel
González Suárez, Eva
Keywords: Càncer de mama
Cicle cel·lular
Breast cancer
Cell cycle
Issue Date: 1-Jan-2021
Publisher: Elsevier Inc.
Abstract: Rank signaling enhances stemness in mouse and human mammary epithelial cells (MECs) and mediates mammary tumor initiation. Mammary tumors initiated by oncogenes or carcinogen exposure display high levels of Rank and Rank pathway inhibitors have emerged as a new strategy for breast cancer prevention and treatment. Here, we show that ectopic Rank expression in the mammary epithelia unexpectedly delays tumor onset and reduces tumor incidence in the oncogene-driven Neu and PyMT models. Mechanistically, we have found that ectopic expression of Rank or exposure to Rankl induces senescence, even in the absence of other oncogenic mutations. Rank leads to DNA damage and senescence through p16/p19. Moreover, RANK-induced senescence is essential for Rank-driven stemness, and although initially translates into delayed tumor growth, eventually promotes tumor progression and metastasis. We uncover a dual role for Rank in the mammary epithelia: Rank induces senescence and stemness, delaying tumor initiation but increasing tumor aggressiveness.
Note: Reproducció del document publicat a:
It is part of: Developmental Cell, 2021, vol. 56
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Appears in Collections:Articles publicats en revistes (Institut d'lnvestigació Biomèdica de Bellvitge (IDIBELL))
Publicacions de projectes de recerca finançats per la UE
Articles publicats en revistes (Institut de Recerca Biomèdica (IRB Barcelona))

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